- Email: [email protected]
Prevalence of Urolithiasis in Asymptomatic Adults: Objective Determination Using Low Dose Noncontrast Computerized Tomography
Urolithiasis/Endourology
Prevalence of Urolithiasis in Asymptomatic Adults: Objective Determination Using Low Dose Noncontrast Computerized Tomography Cody J. Boyce, Perry J. Pickhardt,* Edward M. Lawrence, David H. Kim† and Richard J. Bruce From the University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Purpose: The true prevalence of urolithiasis in asymptomatic adults is unknown. Unenhanced computerized tomography represents the gold standard for detection. We evaluated the prevalence and symptomatic incidence of urolithiasis in a large cohort of asymptomatic adults using noncontrast computerized tomography. Materials and Methods: Low dose noncontrast computerized tomography was performed in 5,047 consecutive asymptomatic adults (mean age 56.9 years, 2,747 women and 2,300 men) between 2004 and 2008. Presence, size and location of urinary calculi were recorded. Screening prevalence as well as the incidence of symptomatic stone disease during a 10-year interval (1997 to 2007) was compared against previously established clinical risk factors. Results: The screening prevalence of asymptomatic urolithiasis was 7.8% (395 of 5,047 adults) with an average of 2.1 stones per case (range 1 to 29) and a mean stone size of 3.0 mm (range 1 to 20). During a 10-year period 20.5% (81 of 395) of patients with stones (1.6% of entire screening cohort) had at least 1 symptomatic episode. Males were more likely to have urolithiasis than females (9.7% vs 6.3%, p ⬍0.001). Diabetes (9.0% vs 7.7%, p ⫽ 0.45), obesity (7.6% vs 7.9%, p ⫽ 0.72) and age 60 years or older (8.0% vs 7.7%, p ⫽ 0.73) did not affect prevalence, but diabetes and obesity did correlate with symptom development (p ⬍0.001 and p ⬍0.05, respectively). Conclusions: This objective population based assessment in a large asymptomatic cohort showed an 8% prevalence of urolithiasis. Most cases were unsuspected and remained asymptomatic. Although there was no correlation between asymptomatic urolithiasis and diabetes, obesity or older age, diabetes and obesity were associated with a higher incidence of symptoms over time.
Abbreviations and Acronyms BMI ⫽ body mass index CT ⫽ computerized tomography CTC ⫽ computerized tomography colonography RF ⫽ risk factor Submitted for publication July 14, 2009. Study received institutional review board approval. * Correspondence: Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave., Madison, Wisconsin 537923252 (telephone: 608-263-8969; FAX: 608-2630140; e-mail: [email protected]). † Financial interest and/or other relationship with Viatronix, MedicSight and VirtuoCTC.
Key Words: prevalence; urolithiasis; calculi; tomography, x-ray computed; risk factors UROLITHIASIS, or urinary stone disease, represents an enormous clinical and financial burden to the United States health care system. Urolithiasis accounts for more than 2 million office visits and nearly 200,000 hospital admissions each year with an estimated annual cost of more than $2 billion in
the United States alone.1 Studies also suggest that the incidence of symptomatic stone disease is increasing.1,2 Despite the obvious importance of this disease the true prevalence has not been established by objective criteria. Previous attempts at establishing prevalence in large scale series
0022-5347/10/1833-1017/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 183, 1017-1021, March 2010 Printed in U.S.A. DOI:10.1016/j.juro.2009.11.047
AND
RESEARCH, INC.
www.jurology.com
1017
1018
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
have used either patient recall or ICD-9 coding, effectively ignoring asymptomatic urolithiasis.2,3 Similarly only limited data exist regarding the incidence of symptomatic disease among all patients with urolithiasis. Although we do know that the recurrence rate for patients with prior symptomatic stone disease exceeds 50%, the incidence of symptomatic transition from an asymptomatic state is unknown.4,5 A host of clinical risk factors have been associated with urolithiasis, including but not limited to age older than 60 years, male gender, diabetes or insulin resistance, increased BMI, as well as a number of specific dietary and urinary factors. Various diagnostic methods have been used for detecting urinary stones including excretory urography, abdominal radiography, sonography, magnetic resonance imaging and CT. However, CT is clearly the diagnostic gold standard with an accuracy that approaches 100% due to the increased attenuation values of urinary calculi.6 – 8 CT not only represents a noninvasive means to identify, quantify, size and locate urinary stones, it can also assess for the presence of obstruction and suggest alternative diagnoses in patients with flank or groin pain.9 In this study we assessed the prevalence of urolithiasis in an asymptomatic United States adult population using low dose noncontrast CT, as well as the development of symptomatic stone disease during a 10-year period. Prevalence of asymptomatic urolithiasis and the onset of symptomatic disease were correlated with reported clinical risk factors.
MATERIALS AND METHODS This Health Insurance Portability and Accountability Act compliant retrospective study was performed under an institutional review board approved protocol. The need for signed informed consent for this investigation was waived. Unenhanced low dose CT was performed on 5,047 consecutive asymptomatic adults undergoing routine CT colonography screening at a single institution during a 4-year interval (between 2004 and 2008) using a clinically validated technique.10,11 The demographic data for this screening cohort are provided in table 1. Because the noncontrast CT imaging for colonography covers the entire urinary system and is equivalent to a CT performed for urolithiasis evaluation, no additional scanning or radiation dose was necessary for this study. The specific low dose noncontrast multidetector CT protocol used in this study has been previously described.10 Table 1. Demographic and clinical characteristics of the screening cohort Mean ⫾ SD age No. age 60 yrs or older (%) No. overwt ⫹ obese (%) No. obese (%) No. diabetes mellitus (%)
56.9 ⫾ 7.3 1,480 (29) 3,296 (65) 1,369 (27) 324 (6)
The effective radiation dose for the supine CT series is approximately 2.5 mSv, which is substantially lower than typical contrast enhanced CT and slightly less than annual background radiation. All studies were performed on 8 or 16-channel multidetector CT scanners (LightSpeed™ series). The extracolonic supine CT images were prospectively reviewed by 1 of 5 abdominal radiologists on a standard picture archiving and communication system workstation at 5 mm thick sections reconstructed at 3 mm intervals. The presence, number, size and location of urinary stone disease was recorded, and subsequently confirmed on retrospective review. Stones were identified by 1 of 5 board certified abdominal radiologists. Care was taken to exclude vascular or other nonstone related calcifications from renal calculi. Demographic data and potential clinical risk factors for urolithiasis were recorded from a combined assessment of the screening intake form (eg age, gender, race, height, weight and BMI) and the electronic medical record (diabetes). Chart review included comprehensive text searches with pertinent ICD-9 code searches to identify diabetic patients. Overweight or obese status was defined as a BMI of 25 kg/m2 or greater and obesity was defined as BMI 30 kg/m2 or greater. The older age group was defined as 60 years or older. The prevalence data among this screening cohort for these clinical risk factors are listed in table 1. Symptomatic stone disease was determined by additional radiological imaging, chart review of pertinent clinical visits, urological emergent or urgent care and pertinent ICD-9 codes. A 10-year time horizon from 1997 to 2007 was included to evaluate the incidence of symptomatic urolithiasis. Patients in whom symptomatic stone disease developed after CT detection were further subcategorized. RF assessment for symptomatic disease was performed. Fisher’s exact test was used to assess demographic and clinical risk factors for the association with urolithiasis.
RESULTS The prevalence of urolithiasis at noncontrast CT in this asymptomatic cohort of 5,047 consecutive adults was 7.8% (395 cases) with a total of 814 calculi identified. Mean stone size was 3.0 mm (range 1 to 20). The distribution of calculi according to number per patient, the largest stone per patient and the overall distribution of stone size are shown in figure 1. The mean number of stones per patient was 2.1, ranging from a single calculus in 243 patients up to 29 stones in 1 patient (fig. 2). Of 395 patients 152 (38.5%) had more than 1 stone but only 16 (4.1%) had more than 5 stones. Only 14 (1.7%) of 814 urinary stones measured 1 cm or larger. Stones were present on the right side in 242 patients and on the left in 239, with bilateral disease in 87. Of the 395 total patients with urinary stones 391 (99.0%) had nephrolithiasis (renal calculi), 6 had ureteral calculi and 2 had bladder calculi. Of the 6 patients with unsuspected asymptomatic ureteral
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
1019
Table 2. Prevalence of asymptomatic urolithiasis
Figure 1. Distribution of total number of stones (A) and largest stone per patient (B) as well as distribution of stone size (C) in asymptomatic screening population.
stones 4 had a component of obstructive hydronephrosis. The relative prevalence of urolithiasis at screening among individuals with purported clinical RFs is shown in table 2. Of the risk factors evaluated male gender was the only one that significantly affected the screening prevalence, with urolithiasis in 9.7% of men (222 of 2,300) vs 6.3% of women (173 of 2,747) (p ⬍0.001). The remaining potential risk factors of diabetes, overweight or obese status and older age did not significantly affect the prevalence of urolithiasis. The incidence of symptomatic urolithiasis during a 10-year interval was 20.5% (81 of 395) of patients with urolithiasis and 1.6% of the entire screening cohort of 5,047 adults. Symptoms developed in 44% (36 of 81) of these patients prospectively after asymptomatic detection at CT with an average interval of 1.3 years (458 days ⫾ 1.1 years). The remaining 45 patients had a symptomatic episode of urolithiasis on record review at some point before asymptomatic CTC screening. RF assessment for symptomatic disease is shown in table 3. There were important differences in asymptomatic screening prevalence vs symptomatic incidence. Although diabetes and obesity were not significant risk factors for
Male gender Diabetes Age 60 yrs or older Obese Overwt ⫹ obese Entire asymptomatic cohort
% Prevalence With RF (No./total No.)
% Prevalence Without RF (No./total No.)
9.7 (222/2,300) 9.0 (29/324) 8.0 (119/1,480) 7.6 (104/1,369) 7.9 (261/3,296)
6.3 (173/2,747) 7.7 (366/4,725) 7.7 (276/3,568) 7.9 (289/3,647) 7.7 (132/1,720) 7.8 (395/5,047)
p Value ⬍0.001 0.45 0.73 0.72 0.78
urolithiasis in general, they were both significantly associated with symptomatic stone disease. Diabetics accounted for 17.3% of symptomatic patients with stones but only 4.8% of patients with stones who remained asymptomatic during the observation period (p ⬍0.001), corresponding to an odds ratio of 4.2 (95% CI 1.9 –9.0). Likewise obese patients accounted for 35.8% of the symptomatic stone cohort compared with 23.9% of the cohort who remained asymptomatic, corresponding to an odds ratio of 1.8 (95% CI 1.1–3.0). In contrast, although male gender was the only identified RF for overall prevalence of urolithiasis at screening, it was not significantly associated with the development of symptoms (table 3).
DISCUSSION Urolithiasis is a common malady in the United States with estimates of associated costs exceeding $2 billion U.S. per year.1 Urinary stone disease may be asymptomatic or result in symptoms that necessitate treatment or intervention, or even lead to serious complications such as pyonephrosis and chronic renal failure.12 Studies suggest that the incidence of urolithiasis is increasing.1,2 Previous attempts to quantify the prevalence of urolithiasis in a large, population level cohort have been largely based on patient recall of symptomatic episodes and medical coding, neither of which allows for the assessment of the true prevalence since most cases are presumably asymptomatic.2,3
Table 3. Incidence of symptomatic urolithiasis according to potential risk factors
Figure 2. Urolithiasis detected at low dose noncontrast CT in asymptomatic adults undergoing screening CTC. CTC images from 2 adults show single 14 mm calculus involving right kidney in 1 individual (A) and multiple smaller bilateral renal calculi in second individual (B).
Male Diabetes Age 60 yrs or older Obese (BMI 30 kg/m2 or greater) Overwt ⫹ obese (BMI 25 kg/m2 or greater)
No. Symptomatic (%)*
No. No Symptoms (%)
p Value
51 (63.0) 14 (17.3) 25 (30.9) 29 (35.8)
171 (54.4) 15 (4.8) 94 (29.9) 75 (23.9)
0.21 ⬍0.001 0.89 ⬍0.05
62 (76.5)
199 (63.4)
0.03
* Symptom development during 10-year observation period.
1020
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
Unenhanced CT represents the diagnostic gold standard for identifying urolithiasis, whether symptomatic or asymptomatic.6 For symptomatic patients with suspected urolithiasis noncontrast CT provides for rapid, accurate, objective and noninvasive assessment.8 In addition, CT readily identifies urodynamically significant obstruction by demonstrating findings of hydronephrosis, perinephric stranding and renal edema.13 Other radiological imaging studies such as excretory urography, abdominal radiography and sonography are significantly less sensitive as well as less specific for diagnosing urolithiasis.7,14 Because noncontrast CT evaluation of the entire urinary system is incidentally assessed at CT colonography screening, it provides an ideal means for determining the true prevalence of urolithiasis in an asymptomatic healthy adult population. Our study found that the prevalence of urolithiasis for an asymptomatic adult population in the Midwest was 7.8%, of whom approximately 20% experienced symptoms during a 10-year interval, nearly half of which occurred following asymptomatic detection at CT. In a distinct but similar age asymptomatic adult cohort of 1,233 individuals (mean age 57.8 years) from the east and west coasts of the United States we incidentally noted a remarkably similar 7.9% prevalence of urolithiasis.11 Smaller studies of renal donor patients also corroborate our findings,15,16 suggesting that this screening prevalence in asymptomatic adults may represent a generalizable result. Previous estimates of urolithiasis based on patient recall or medical coding will reflect only symptomatic disease due to the nature of the determination. According to patient recall of symptomatic episodes 1 study estimated the prevalence of urolithiasis to be 5%.2 Another study estimated a 5% prevalence for females and 12% prevalence for males using a medical coding method.3 Previous attempts to establish the incidence of symptom development from urinary stone disease were also limited by the fact that the underlying prevalence of urolithiasis (symptomatic and asymptomatic) has not been truly established. A metaanalysis of studies of symptom recurrence in patients with a history of prior stone disease found a 10-year recurrence rate of 52%.5 However, this finding largely reflects the recurrence rate of previously symptomatic disease and effectively ignores the larger group of individuals with asymptomatic urolithiasis due to lack of detection. Our study provides this missing information by identifying this larger group with stones but without symptoms. CT colonography screening of asymptomatic adults provides a unique opportunity to gather such data. In our study the 10-year incidence of symptomatic disease in adults with urolithiasis at CT colonography screening was 20.5%, or 1.6% of the entire screening cohort. Not
surprisingly the relative incidence of symptomatic disease is less when individuals who have never experienced symptoms previously are included. It could be argued that individuals with incidentally detected stones could be treated more conservatively compared with those who have already had symptoms in the past. It is interesting to note that several established clinical risk factors, namely diabetes, obesity and age, did not show a significant increase in the screening prevalence of asymptomatic urolithiasis in our study. However, diabetes and obesity were associated with a higher likelihood of symptom development from stones, which corresponds to what was previously measurable (ie the underlying rate of asymptomatic urolithiasis was not included). Male gender showed only a modestly increased risk for symptom development, which was not statistically significant. However, because male gender showed a significantly higher underlying screening prevalence, this combination still led to a higher overall rate of previously detectable (ie symptomatic) urolithiasis. The extracolonic evaluation provided by CT colonography screening raises some important issues. The low dose, noncontrast CT technique provides a nondiagnostic evaluation of most structures but still can detect unsuspected extracolonic cancers, abdominal aortic aneurysms and even genetic conditions (eg autosomal dominant polycystic kidney disease and hemochromatosis).17 In conjunction with colorectal cancer screening this extracolonic evaluation can be clinically effective and cost-effective if handled properly.18 However, extracolonic findings can also lead to further evaluation for findings that ultimately prove to be of no real clinical significance. In the case of urolithiasis the noncontrast technique used for CT colonography fortuitously provides an optimal evaluation for urolithiasis. Given that approximately 8% of United States adults older than 50 years may have nonobstructing renal calculi, unsuspected stones will be frequently identified at diagnostic CT in patients presenting with nonspecific abdominal pain. If no other identifiable etiology for pain is identified by CT, it may be tempting to implicate the incidental urolithiasis as a potential cause. In fact, 1 study has suggested that nonobstructing renal stones may be the cause of the presenting abdominal pain in such cases.19 However, given the relatively high prevalence of incidental asymptomatic urolithiasis in our study of more than 5,000 adults, we believe that assigning causality may be fraught with error. The appropriate treatment of patients with these asymptomatic stones found incidentally at imaging remains uncertain. Because of the high asymptomatic prevalence and relatively low rate of symptomatic conversion within
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
the entire cohort, initial conservative management may be appropriate, except for patients with a large stone burden, obstruction or comorbidities such as diabetes. Further investigation into the most appropriate clinical management of unsuspected urolithiasis is warranted. There are several limitations to our study. The study cohort was largely focused on adults older than 50 years, with only 31 younger than 40 years. Study participants were selected because they had undergone CTC screening, potentially reflecting a more health conscious subset of the general United States adult population. Although it is conceivable that some cases of renal parenchymal or vascular calcification could have been counted as stone disease, image interpretation was performed by experienced abdominal radiologists and this distinction is usually straightforward. Because of the retrospective nature of the study we were unable to assess all known clinical risk factors for urinary stone formation (such as diet, fluid intake and prior urinary tract infection). In addition, the 10-year symptomatic observation window included some episodes which preceded the CTC examination. However, this symptomatic cohort which reverted to asymptomatic status at the time of CTC is likely similar to the postCTC symptomatic cohort and, therefore, distinct from the larger, previously unmeasured asymptomatic
1021
group. The 10-year observation period was included to obtain a longer term assessment for symptomatic disease. Finally our assessment of symptomatic stone disease by extensive medical records review may not have accounted for all symptomatic episodes in this large cohort because such searches are not infallible.
CONCLUSIONS Urolithiasis is a prevalent condition with substantial clinical and financial costs associated with symptomatic disease. Noncontrast CT is a reliable, objective and noninvasive test for detecting urinary stones, and represents the diagnostic gold standard. By evaluating an asymptomatic screening population our study provides new insight into the true prevalence of urolithiasis through comprehensive inclusion of asymptomatic disease. We also found that approximately 1 in 5 adults with asymptomatic urolithiasis will experience symptoms during a 10-year period, which is considerably less than published recurrence rates in previously symptomatic cases but is nonetheless substantial. Our findings are also remarkable in that some previously established clinical RFs, namely diabetes and obesity, do not appear to meaningfully impact the overall prevalence of asymptomatic urolithiasis but are associated with symptomatic disease.
REFERENCES 1. Pearle MS, Calhoun EA and Curhan GC: Urologic Diseases in America Project: urolithiasis. J Urol 2005; 173: 848.
8. Smith RC, Verga M, McCarthy S et al: Diagnosis of acute flank pain: value of unenhanced helical CT. AJR Am J Roentgenol 1996; 166: 97.
14. Ulusan S, Koc Z and Tokmak N: Accuracy of sonography for detecting renal stone: comparison with CT. J Clin Ultrasound 2007; 35: 256.
2. Stamatelou KK, Francis ME, Jones CA et al: Time trends in reported prevalence of kidney stones in the United States: 1976 –1994. Kidney Int 2003; 63: 1817.
9. Rucker CM, Menias CO and Bhalla S: Mimics of renal colic: alternative diagnoses at unenhanced helical CT. Radiographics 2004; 24: S11.
15. Platt JF, Ellis JH, Korobkin M et al: Helical CT evaluation of potential kidney donors: findings in 154 subjects. AJR Am J Roentgenol 1997; 169: 1325.
10. Kim DH, Pickhardt PJ, Taylor AJ et al: CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med 2007; 357: 1403.
16. Strang AM, Lockhart ME, Kenney PJ et al: Computerized tomographic angiography for renal donor evaluation leads to a higher exclusion rate. J Urol 2007; 177: 1826.
3. Johnson CM, Wilson DM, O’Fallon WM et al: Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int 1979; 16: 624. 4. Sutherland JW, Parks JH and Coe FL: Recurrence after a single renal stone in a community practice. Miner Electrolyte Metab 1985; 11: 267. 5. Uribarri J, Oh MS and Carroll HJ: The first kidney stone. Ann Intern Med 1989; 111: 1006.
11. Pickhardt PJ, Choi JR, Hwang I et al: Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003; 349: 2191.
17. Pickhardt PJ, Hanson ME, Vanness DJ et al: Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology 2008; 249: 151.
6. Preminger GM, Vieweg J, Leder RA et al: Urolithiasis: detection and management with unenhanced spiral CT–a urologic perspective. Radiology 1998; 207: 308.
12. Jungers P, Joly D, Barbey F et al: ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention. Am J Kidney Dis 2004; 44: 799.
18. Hassan C, Pickhardt PJ, Laghi A et al: Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis. Arch Intern Med 2008; 168: 696.
7. Smith RC, Rosenfield AT, Choe KA et al: Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography. Radiology 1995; 194: 789.
13. Dalrymple NC, Casford B, Raiken DP et al: Pearls and pitfalls in the diagnosis of ureterolithiasis with unenhanced helical CT. Radiographics 2000; 20: 439.
19. Furlan A, Federle MP, Yealy DM et al: Nonobstructing renal stones on unenhanced CT: a real cause for renal colic? AJR Am J Roentgenol 2008; 190: W125.
Prevalence of Urolithiasis in Asymptomatic Adults: Objective Determination Using Low Dose Noncontrast Computerized Tomography Cody J. Boyce, Perry J. Pickhardt,* Edward M. Lawrence, David H. Kim† and Richard J. Bruce From the University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Purpose: The true prevalence of urolithiasis in asymptomatic adults is unknown. Unenhanced computerized tomography represents the gold standard for detection. We evaluated the prevalence and symptomatic incidence of urolithiasis in a large cohort of asymptomatic adults using noncontrast computerized tomography. Materials and Methods: Low dose noncontrast computerized tomography was performed in 5,047 consecutive asymptomatic adults (mean age 56.9 years, 2,747 women and 2,300 men) between 2004 and 2008. Presence, size and location of urinary calculi were recorded. Screening prevalence as well as the incidence of symptomatic stone disease during a 10-year interval (1997 to 2007) was compared against previously established clinical risk factors. Results: The screening prevalence of asymptomatic urolithiasis was 7.8% (395 of 5,047 adults) with an average of 2.1 stones per case (range 1 to 29) and a mean stone size of 3.0 mm (range 1 to 20). During a 10-year period 20.5% (81 of 395) of patients with stones (1.6% of entire screening cohort) had at least 1 symptomatic episode. Males were more likely to have urolithiasis than females (9.7% vs 6.3%, p ⬍0.001). Diabetes (9.0% vs 7.7%, p ⫽ 0.45), obesity (7.6% vs 7.9%, p ⫽ 0.72) and age 60 years or older (8.0% vs 7.7%, p ⫽ 0.73) did not affect prevalence, but diabetes and obesity did correlate with symptom development (p ⬍0.001 and p ⬍0.05, respectively). Conclusions: This objective population based assessment in a large asymptomatic cohort showed an 8% prevalence of urolithiasis. Most cases were unsuspected and remained asymptomatic. Although there was no correlation between asymptomatic urolithiasis and diabetes, obesity or older age, diabetes and obesity were associated with a higher incidence of symptoms over time.
Abbreviations and Acronyms BMI ⫽ body mass index CT ⫽ computerized tomography CTC ⫽ computerized tomography colonography RF ⫽ risk factor Submitted for publication July 14, 2009. Study received institutional review board approval. * Correspondence: Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave., Madison, Wisconsin 537923252 (telephone: 608-263-8969; FAX: 608-2630140; e-mail: [email protected]). † Financial interest and/or other relationship with Viatronix, MedicSight and VirtuoCTC.
Key Words: prevalence; urolithiasis; calculi; tomography, x-ray computed; risk factors UROLITHIASIS, or urinary stone disease, represents an enormous clinical and financial burden to the United States health care system. Urolithiasis accounts for more than 2 million office visits and nearly 200,000 hospital admissions each year with an estimated annual cost of more than $2 billion in
the United States alone.1 Studies also suggest that the incidence of symptomatic stone disease is increasing.1,2 Despite the obvious importance of this disease the true prevalence has not been established by objective criteria. Previous attempts at establishing prevalence in large scale series
0022-5347/10/1833-1017/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 183, 1017-1021, March 2010 Printed in U.S.A. DOI:10.1016/j.juro.2009.11.047
AND
RESEARCH, INC.
www.jurology.com
1017
1018
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
have used either patient recall or ICD-9 coding, effectively ignoring asymptomatic urolithiasis.2,3 Similarly only limited data exist regarding the incidence of symptomatic disease among all patients with urolithiasis. Although we do know that the recurrence rate for patients with prior symptomatic stone disease exceeds 50%, the incidence of symptomatic transition from an asymptomatic state is unknown.4,5 A host of clinical risk factors have been associated with urolithiasis, including but not limited to age older than 60 years, male gender, diabetes or insulin resistance, increased BMI, as well as a number of specific dietary and urinary factors. Various diagnostic methods have been used for detecting urinary stones including excretory urography, abdominal radiography, sonography, magnetic resonance imaging and CT. However, CT is clearly the diagnostic gold standard with an accuracy that approaches 100% due to the increased attenuation values of urinary calculi.6 – 8 CT not only represents a noninvasive means to identify, quantify, size and locate urinary stones, it can also assess for the presence of obstruction and suggest alternative diagnoses in patients with flank or groin pain.9 In this study we assessed the prevalence of urolithiasis in an asymptomatic United States adult population using low dose noncontrast CT, as well as the development of symptomatic stone disease during a 10-year period. Prevalence of asymptomatic urolithiasis and the onset of symptomatic disease were correlated with reported clinical risk factors.
MATERIALS AND METHODS This Health Insurance Portability and Accountability Act compliant retrospective study was performed under an institutional review board approved protocol. The need for signed informed consent for this investigation was waived. Unenhanced low dose CT was performed on 5,047 consecutive asymptomatic adults undergoing routine CT colonography screening at a single institution during a 4-year interval (between 2004 and 2008) using a clinically validated technique.10,11 The demographic data for this screening cohort are provided in table 1. Because the noncontrast CT imaging for colonography covers the entire urinary system and is equivalent to a CT performed for urolithiasis evaluation, no additional scanning or radiation dose was necessary for this study. The specific low dose noncontrast multidetector CT protocol used in this study has been previously described.10 Table 1. Demographic and clinical characteristics of the screening cohort Mean ⫾ SD age No. age 60 yrs or older (%) No. overwt ⫹ obese (%) No. obese (%) No. diabetes mellitus (%)
56.9 ⫾ 7.3 1,480 (29) 3,296 (65) 1,369 (27) 324 (6)
The effective radiation dose for the supine CT series is approximately 2.5 mSv, which is substantially lower than typical contrast enhanced CT and slightly less than annual background radiation. All studies were performed on 8 or 16-channel multidetector CT scanners (LightSpeed™ series). The extracolonic supine CT images were prospectively reviewed by 1 of 5 abdominal radiologists on a standard picture archiving and communication system workstation at 5 mm thick sections reconstructed at 3 mm intervals. The presence, number, size and location of urinary stone disease was recorded, and subsequently confirmed on retrospective review. Stones were identified by 1 of 5 board certified abdominal radiologists. Care was taken to exclude vascular or other nonstone related calcifications from renal calculi. Demographic data and potential clinical risk factors for urolithiasis were recorded from a combined assessment of the screening intake form (eg age, gender, race, height, weight and BMI) and the electronic medical record (diabetes). Chart review included comprehensive text searches with pertinent ICD-9 code searches to identify diabetic patients. Overweight or obese status was defined as a BMI of 25 kg/m2 or greater and obesity was defined as BMI 30 kg/m2 or greater. The older age group was defined as 60 years or older. The prevalence data among this screening cohort for these clinical risk factors are listed in table 1. Symptomatic stone disease was determined by additional radiological imaging, chart review of pertinent clinical visits, urological emergent or urgent care and pertinent ICD-9 codes. A 10-year time horizon from 1997 to 2007 was included to evaluate the incidence of symptomatic urolithiasis. Patients in whom symptomatic stone disease developed after CT detection were further subcategorized. RF assessment for symptomatic disease was performed. Fisher’s exact test was used to assess demographic and clinical risk factors for the association with urolithiasis.
RESULTS The prevalence of urolithiasis at noncontrast CT in this asymptomatic cohort of 5,047 consecutive adults was 7.8% (395 cases) with a total of 814 calculi identified. Mean stone size was 3.0 mm (range 1 to 20). The distribution of calculi according to number per patient, the largest stone per patient and the overall distribution of stone size are shown in figure 1. The mean number of stones per patient was 2.1, ranging from a single calculus in 243 patients up to 29 stones in 1 patient (fig. 2). Of 395 patients 152 (38.5%) had more than 1 stone but only 16 (4.1%) had more than 5 stones. Only 14 (1.7%) of 814 urinary stones measured 1 cm or larger. Stones were present on the right side in 242 patients and on the left in 239, with bilateral disease in 87. Of the 395 total patients with urinary stones 391 (99.0%) had nephrolithiasis (renal calculi), 6 had ureteral calculi and 2 had bladder calculi. Of the 6 patients with unsuspected asymptomatic ureteral
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
1019
Table 2. Prevalence of asymptomatic urolithiasis
Figure 1. Distribution of total number of stones (A) and largest stone per patient (B) as well as distribution of stone size (C) in asymptomatic screening population.
stones 4 had a component of obstructive hydronephrosis. The relative prevalence of urolithiasis at screening among individuals with purported clinical RFs is shown in table 2. Of the risk factors evaluated male gender was the only one that significantly affected the screening prevalence, with urolithiasis in 9.7% of men (222 of 2,300) vs 6.3% of women (173 of 2,747) (p ⬍0.001). The remaining potential risk factors of diabetes, overweight or obese status and older age did not significantly affect the prevalence of urolithiasis. The incidence of symptomatic urolithiasis during a 10-year interval was 20.5% (81 of 395) of patients with urolithiasis and 1.6% of the entire screening cohort of 5,047 adults. Symptoms developed in 44% (36 of 81) of these patients prospectively after asymptomatic detection at CT with an average interval of 1.3 years (458 days ⫾ 1.1 years). The remaining 45 patients had a symptomatic episode of urolithiasis on record review at some point before asymptomatic CTC screening. RF assessment for symptomatic disease is shown in table 3. There were important differences in asymptomatic screening prevalence vs symptomatic incidence. Although diabetes and obesity were not significant risk factors for
Male gender Diabetes Age 60 yrs or older Obese Overwt ⫹ obese Entire asymptomatic cohort
% Prevalence With RF (No./total No.)
% Prevalence Without RF (No./total No.)
9.7 (222/2,300) 9.0 (29/324) 8.0 (119/1,480) 7.6 (104/1,369) 7.9 (261/3,296)
6.3 (173/2,747) 7.7 (366/4,725) 7.7 (276/3,568) 7.9 (289/3,647) 7.7 (132/1,720) 7.8 (395/5,047)
p Value ⬍0.001 0.45 0.73 0.72 0.78
urolithiasis in general, they were both significantly associated with symptomatic stone disease. Diabetics accounted for 17.3% of symptomatic patients with stones but only 4.8% of patients with stones who remained asymptomatic during the observation period (p ⬍0.001), corresponding to an odds ratio of 4.2 (95% CI 1.9 –9.0). Likewise obese patients accounted for 35.8% of the symptomatic stone cohort compared with 23.9% of the cohort who remained asymptomatic, corresponding to an odds ratio of 1.8 (95% CI 1.1–3.0). In contrast, although male gender was the only identified RF for overall prevalence of urolithiasis at screening, it was not significantly associated with the development of symptoms (table 3).
DISCUSSION Urolithiasis is a common malady in the United States with estimates of associated costs exceeding $2 billion U.S. per year.1 Urinary stone disease may be asymptomatic or result in symptoms that necessitate treatment or intervention, or even lead to serious complications such as pyonephrosis and chronic renal failure.12 Studies suggest that the incidence of urolithiasis is increasing.1,2 Previous attempts to quantify the prevalence of urolithiasis in a large, population level cohort have been largely based on patient recall of symptomatic episodes and medical coding, neither of which allows for the assessment of the true prevalence since most cases are presumably asymptomatic.2,3
Table 3. Incidence of symptomatic urolithiasis according to potential risk factors
Figure 2. Urolithiasis detected at low dose noncontrast CT in asymptomatic adults undergoing screening CTC. CTC images from 2 adults show single 14 mm calculus involving right kidney in 1 individual (A) and multiple smaller bilateral renal calculi in second individual (B).
Male Diabetes Age 60 yrs or older Obese (BMI 30 kg/m2 or greater) Overwt ⫹ obese (BMI 25 kg/m2 or greater)
No. Symptomatic (%)*
No. No Symptoms (%)
p Value
51 (63.0) 14 (17.3) 25 (30.9) 29 (35.8)
171 (54.4) 15 (4.8) 94 (29.9) 75 (23.9)
0.21 ⬍0.001 0.89 ⬍0.05
62 (76.5)
199 (63.4)
0.03
* Symptom development during 10-year observation period.
1020
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
Unenhanced CT represents the diagnostic gold standard for identifying urolithiasis, whether symptomatic or asymptomatic.6 For symptomatic patients with suspected urolithiasis noncontrast CT provides for rapid, accurate, objective and noninvasive assessment.8 In addition, CT readily identifies urodynamically significant obstruction by demonstrating findings of hydronephrosis, perinephric stranding and renal edema.13 Other radiological imaging studies such as excretory urography, abdominal radiography and sonography are significantly less sensitive as well as less specific for diagnosing urolithiasis.7,14 Because noncontrast CT evaluation of the entire urinary system is incidentally assessed at CT colonography screening, it provides an ideal means for determining the true prevalence of urolithiasis in an asymptomatic healthy adult population. Our study found that the prevalence of urolithiasis for an asymptomatic adult population in the Midwest was 7.8%, of whom approximately 20% experienced symptoms during a 10-year interval, nearly half of which occurred following asymptomatic detection at CT. In a distinct but similar age asymptomatic adult cohort of 1,233 individuals (mean age 57.8 years) from the east and west coasts of the United States we incidentally noted a remarkably similar 7.9% prevalence of urolithiasis.11 Smaller studies of renal donor patients also corroborate our findings,15,16 suggesting that this screening prevalence in asymptomatic adults may represent a generalizable result. Previous estimates of urolithiasis based on patient recall or medical coding will reflect only symptomatic disease due to the nature of the determination. According to patient recall of symptomatic episodes 1 study estimated the prevalence of urolithiasis to be 5%.2 Another study estimated a 5% prevalence for females and 12% prevalence for males using a medical coding method.3 Previous attempts to establish the incidence of symptom development from urinary stone disease were also limited by the fact that the underlying prevalence of urolithiasis (symptomatic and asymptomatic) has not been truly established. A metaanalysis of studies of symptom recurrence in patients with a history of prior stone disease found a 10-year recurrence rate of 52%.5 However, this finding largely reflects the recurrence rate of previously symptomatic disease and effectively ignores the larger group of individuals with asymptomatic urolithiasis due to lack of detection. Our study provides this missing information by identifying this larger group with stones but without symptoms. CT colonography screening of asymptomatic adults provides a unique opportunity to gather such data. In our study the 10-year incidence of symptomatic disease in adults with urolithiasis at CT colonography screening was 20.5%, or 1.6% of the entire screening cohort. Not
surprisingly the relative incidence of symptomatic disease is less when individuals who have never experienced symptoms previously are included. It could be argued that individuals with incidentally detected stones could be treated more conservatively compared with those who have already had symptoms in the past. It is interesting to note that several established clinical risk factors, namely diabetes, obesity and age, did not show a significant increase in the screening prevalence of asymptomatic urolithiasis in our study. However, diabetes and obesity were associated with a higher likelihood of symptom development from stones, which corresponds to what was previously measurable (ie the underlying rate of asymptomatic urolithiasis was not included). Male gender showed only a modestly increased risk for symptom development, which was not statistically significant. However, because male gender showed a significantly higher underlying screening prevalence, this combination still led to a higher overall rate of previously detectable (ie symptomatic) urolithiasis. The extracolonic evaluation provided by CT colonography screening raises some important issues. The low dose, noncontrast CT technique provides a nondiagnostic evaluation of most structures but still can detect unsuspected extracolonic cancers, abdominal aortic aneurysms and even genetic conditions (eg autosomal dominant polycystic kidney disease and hemochromatosis).17 In conjunction with colorectal cancer screening this extracolonic evaluation can be clinically effective and cost-effective if handled properly.18 However, extracolonic findings can also lead to further evaluation for findings that ultimately prove to be of no real clinical significance. In the case of urolithiasis the noncontrast technique used for CT colonography fortuitously provides an optimal evaluation for urolithiasis. Given that approximately 8% of United States adults older than 50 years may have nonobstructing renal calculi, unsuspected stones will be frequently identified at diagnostic CT in patients presenting with nonspecific abdominal pain. If no other identifiable etiology for pain is identified by CT, it may be tempting to implicate the incidental urolithiasis as a potential cause. In fact, 1 study has suggested that nonobstructing renal stones may be the cause of the presenting abdominal pain in such cases.19 However, given the relatively high prevalence of incidental asymptomatic urolithiasis in our study of more than 5,000 adults, we believe that assigning causality may be fraught with error. The appropriate treatment of patients with these asymptomatic stones found incidentally at imaging remains uncertain. Because of the high asymptomatic prevalence and relatively low rate of symptomatic conversion within
PREVALENCE OF UROLITHIASIS IN ASYMPTOMATIC ADULTS
the entire cohort, initial conservative management may be appropriate, except for patients with a large stone burden, obstruction or comorbidities such as diabetes. Further investigation into the most appropriate clinical management of unsuspected urolithiasis is warranted. There are several limitations to our study. The study cohort was largely focused on adults older than 50 years, with only 31 younger than 40 years. Study participants were selected because they had undergone CTC screening, potentially reflecting a more health conscious subset of the general United States adult population. Although it is conceivable that some cases of renal parenchymal or vascular calcification could have been counted as stone disease, image interpretation was performed by experienced abdominal radiologists and this distinction is usually straightforward. Because of the retrospective nature of the study we were unable to assess all known clinical risk factors for urinary stone formation (such as diet, fluid intake and prior urinary tract infection). In addition, the 10-year symptomatic observation window included some episodes which preceded the CTC examination. However, this symptomatic cohort which reverted to asymptomatic status at the time of CTC is likely similar to the postCTC symptomatic cohort and, therefore, distinct from the larger, previously unmeasured asymptomatic
1021
group. The 10-year observation period was included to obtain a longer term assessment for symptomatic disease. Finally our assessment of symptomatic stone disease by extensive medical records review may not have accounted for all symptomatic episodes in this large cohort because such searches are not infallible.
CONCLUSIONS Urolithiasis is a prevalent condition with substantial clinical and financial costs associated with symptomatic disease. Noncontrast CT is a reliable, objective and noninvasive test for detecting urinary stones, and represents the diagnostic gold standard. By evaluating an asymptomatic screening population our study provides new insight into the true prevalence of urolithiasis through comprehensive inclusion of asymptomatic disease. We also found that approximately 1 in 5 adults with asymptomatic urolithiasis will experience symptoms during a 10-year period, which is considerably less than published recurrence rates in previously symptomatic cases but is nonetheless substantial. Our findings are also remarkable in that some previously established clinical RFs, namely diabetes and obesity, do not appear to meaningfully impact the overall prevalence of asymptomatic urolithiasis but are associated with symptomatic disease.
REFERENCES 1. Pearle MS, Calhoun EA and Curhan GC: Urologic Diseases in America Project: urolithiasis. J Urol 2005; 173: 848.
8. Smith RC, Verga M, McCarthy S et al: Diagnosis of acute flank pain: value of unenhanced helical CT. AJR Am J Roentgenol 1996; 166: 97.
14. Ulusan S, Koc Z and Tokmak N: Accuracy of sonography for detecting renal stone: comparison with CT. J Clin Ultrasound 2007; 35: 256.
2. Stamatelou KK, Francis ME, Jones CA et al: Time trends in reported prevalence of kidney stones in the United States: 1976 –1994. Kidney Int 2003; 63: 1817.
9. Rucker CM, Menias CO and Bhalla S: Mimics of renal colic: alternative diagnoses at unenhanced helical CT. Radiographics 2004; 24: S11.
15. Platt JF, Ellis JH, Korobkin M et al: Helical CT evaluation of potential kidney donors: findings in 154 subjects. AJR Am J Roentgenol 1997; 169: 1325.
10. Kim DH, Pickhardt PJ, Taylor AJ et al: CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med 2007; 357: 1403.
16. Strang AM, Lockhart ME, Kenney PJ et al: Computerized tomographic angiography for renal donor evaluation leads to a higher exclusion rate. J Urol 2007; 177: 1826.
3. Johnson CM, Wilson DM, O’Fallon WM et al: Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int 1979; 16: 624. 4. Sutherland JW, Parks JH and Coe FL: Recurrence after a single renal stone in a community practice. Miner Electrolyte Metab 1985; 11: 267. 5. Uribarri J, Oh MS and Carroll HJ: The first kidney stone. Ann Intern Med 1989; 111: 1006.
11. Pickhardt PJ, Choi JR, Hwang I et al: Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003; 349: 2191.
17. Pickhardt PJ, Hanson ME, Vanness DJ et al: Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology 2008; 249: 151.
6. Preminger GM, Vieweg J, Leder RA et al: Urolithiasis: detection and management with unenhanced spiral CT–a urologic perspective. Radiology 1998; 207: 308.
12. Jungers P, Joly D, Barbey F et al: ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention. Am J Kidney Dis 2004; 44: 799.
18. Hassan C, Pickhardt PJ, Laghi A et al: Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis. Arch Intern Med 2008; 168: 696.
7. Smith RC, Rosenfield AT, Choe KA et al: Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography. Radiology 1995; 194: 789.
13. Dalrymple NC, Casford B, Raiken DP et al: Pearls and pitfalls in the diagnosis of ureterolithiasis with unenhanced helical CT. Radiographics 2000; 20: 439.
19. Furlan A, Federle MP, Yealy DM et al: Nonobstructing renal stones on unenhanced CT: a real cause for renal colic? AJR Am J Roentgenol 2008; 190: W125.